Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression

Ji Hye Yang, Nam Hee Kim, Jun Seop Yun, Eunae Sandra Cho, Yong Hoon Cha, Sue Bean Cho, Seon Hyeong Lee, So Young Cha, Soo Youl Kim, Jiwon Choi, Tin Tin Manh Nguyen, Sunghyouk Park, Hyun Sil Kim, Jong In Yook

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic metabolism are not well defined. In this study, we observe that Snail (SNAI1), a key transcriptional repressor of epithelial-mesenchymal transition, enhances catabolic FAO, allowing pro-survival of breast cancer cells in a starved environment. Mechanistically, Snail suppresses mitochondrial ACC2 (ACACB) by binding to a series of E-boxes located in its proximal promoter, resulting in decreased malonyl-CoA level. Malonyl-CoA being a well-known endogenous inhibitor of fatty acid transporter carnitine palmitoyltransferase 1 (CPT1), the suppression of ACC2 by Snail activates CPT1-dependent FAO, generating ATP and decreasing NADPH consumption. Importantly, combinatorial pharmacologic inhibition of pentose phosphate pathway and FAO with clinically available drugs efficiently reverts Snail-mediated metabolic reprogramming and suppresses in vivo metastatic progression of breast cancer cells. Our observations provide not only a mechanistic link between epithelial-mesenchymal transition and catabolic rewiring but also a novel catabolism-based therapeutic approach for inhibition of cancer progression.

Original languageEnglish
Article numbere202000683
JournalLife Science Alliance
Issue number7
Publication statusPublished - 2020 Jun 2

Bibliographical note

Publisher Copyright:
© 2020 Yang et al.

All Science Journal Classification (ASJC) codes

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis


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